More than half of all US adults are overweight or obese, and over 5% of US health expenditures are directed at medical costs associated with obesity. We have recently reported, in a cohort of 842 women aged 43-55, dramatic differences in reproductive hormone patterns in ovulatory overweight and obese women, compared to women with a body mass index less than 25 kg/m2, during the early stages of the menopausal transition. These changes include longer and more irregular cycles, and decreased LH, FSH, estradiol and luteal progesterone metabolite excretion in urine over the course of an entire menstrual cycle. These alterations in menstrual cycle hormones may represent chronic, weight related changes, and may play a role in the morbidity of obesity, We propose to test the hypothesis that weight loss in obese women will result in normalization of reproductive hormones and to determine potential mechanisms for this salutary effect. We propose to determine the acute and chronic effects of a large weight reduction (at least 25% reductions from mean starting weight) in 30 morbidly obese women aged 35-50 who are scheduled to undergo gastric bypass surgery on daily reproductive hormone patterns, folliculogenesis, central neural GnRH drive and adipokines. We will examine whole cycle reproductive hormone patterns; early follicular phase pulsatile LH secretory patterns; serial transvaginal ultrasounds for one cycle or up to 25 days; and leptin, adiponectin and TNF alpha serum levels before, and at two time points after, gastric bypass. Demonstration of the reversibility of obesity related changes in menstrual cyclicity would provide support for the conduct of a randomized, clinical trial, and the proposed detailed monitoring can be used to provide important clues to the mechanisms by which the acute and chronic reversal of obesity impacts upon female reproduction. Thus, this initial exploration, if positive, would provide the basis for a new line of investigation for the PI into the interactions between reproduction and metabolism.